Autologous bone marrow transplantation (BMT) is currently under evaluation as an alternative approach to allogeneic BMT for the treatment of acute lymphoblastic leukemia (ALL) patients who do not possess matched sibling donors. However, the frequent occurrence of residual leukemia in the remission marrow is a major limitation to the use of autologous BMT. This difficulty makes ex vivo purging of autologous stem cell grafts prior to transplantation essential for therapeutic efficacy. Current ex vivo purging strategies involve the treatment of autologous marrow with cyclophosphamide congeners, monoclonal antibodies (MoAb) plus complement and cytotoxic chemicals bound to MoAb's (immunotoxins). Despite such ex vivo manipulations of autologous stem cell grafts, recurrent leukemia in autotransplanted patients remains the major cause for treatment failure in ALL.
Presently it cannot be determined whether such relapses occur because of incomplete purging of the marrow or incomplete eradication of leukemia in the patients. Present clinical trials usually rely on preclinical studies in which the efficacy of purgative reagents is evaluated against tumor cell lines established in vitro. However, there is a marked heterogeneity in surface antigen expression among leukemia cell populations and neither the phenotype nor the drug or toxin sensitivity of leukemic progenitor cells has been determined. For example, it is believed that none of the monoclonal antibodies or immunotoxins which are currently under clinical evaluation have been tested directly against clonogenic blasts (CFU-L) from ALL patients, and therefore there is no evidence that they can effectively eliminate leukemic progenitor cells.
Therefore a need exists for a monoclonal antibody which is highly specific for ALL progenitor cells while exhibiting no significant binding to pluripotent bone marrow cells. Such a monoclonal antibody could provide the basis for an immunotoxin effective to eliminate leukemic progenitor cells while exhibiting little or no toxicity to normal bone marrow progenitor cells.